5324
J . Org. C h e m . 1994,59,5324-5327
2-(Triphenylphosphonio)-4,5-bis(benzoylthio)1,3-dithiole Tetrafluoroborate: A Versatile Wittig Reagent for the Synthesis of Unsymmetrical Tetrathiafulvalenes and 1,3-Dithiol-2-ylidene Derivatives Thomas K. Hamen,*!+Martin R. Bryce,* Judith A. K. Howard, and Dimitri S. Yufit Department of Chemistry, University of D u r h a m , Durham DH1 3LE,
U.K.
Received October 27, 1993@
The title Wittig reagent 5 has been prepared in three steps (84% overall yield) from 4,5-bis(benzoylthio)-l,3-dithiole-2-thione.Reactions of ylide 7, generated by treatment of 5 with diisopropylethylamine a t room temperature, have been exploited in the synthesis of new unsymmetrical tetrathiafulvalenes and 1,3-dithiol-2-ylidene derivatives. Subsequent removal of the benzoyl protecting group with sodium ethoxide liberates the transient TTF-dithiolate or 1,3dithiole-dithiolate anions which can be alkylated in situ. The X-ray crystal structures of compounds 17 and 18 are reported: close nonbonded S-0 intramolecular interactions are observed in both structures. Since the initial reports that tetrathiafulvalene formed stable cation salts possessing unusual electronic properties (e.g., organic metalsll compounds containing the 1,3dithiol-2-ylidene unit have received unabated attention.2 The important properties of the 1,3-dithiole ring system that render it a particularly attractive building block for new materials are as follows:2(i)the ring system can be easily constructed with a range of functional groups (including fused rings) present in the 4,5 positions; (ii) the system is readily oxidized to the stable six n-electron 1,3-dithiolium cation species (cf. the TTF cation radical species responsible for high conductivity); (iii)the presence of sulfur atoms and the planarity of the 1,3dithiolium cation assists in close intermolecular interactions in the solid state due to n-n overlap. A combination of these properties has resulted in 1,3dithiol-2-ylidene units being a key structural feature in many new n-electron donor^,^ conducting polymers? Langmuir-Blodgett film material^,^ sensors,6 molecular shuttles,’ as well as potential nonlinear optical,* and ferromagnetic material^.^ The aim of the present study was to synthesize the title Wittig-reagent 5 (Scheme 1)and to explore the reactivity of ylide 7 (Scheme 2) in the preparation of new tetrathiafulvalenes and 1,3-dithiol-2-ylidenesystems. The special feature of reagent 5 is that the benzoyl protecting +Visiting scientist from University of Odense, Department of Chemistry, 5230 Odense M, Denmark. Present address: Novo-Nordisk Park, D9-2.03,2760 Maaloev, Denmark. Abstract published in Advance ACS Abstracts, August 1, 1994. (1)Wudl, F.; Smith, G. M.; Hufhagel, E. J. J. Chem. SOC.;Chem. Commun. 1970,1453. (b) Ferraris, J.; Cowan, D. 0.;Walatka, V. V.; Perlsten, J. H. J.Am. Chem. SOC.1973,95,948. (2) Hansen, T. K.; Becher, J. Adu. Mater. 1993,5,288. (3)(a) Sugimoto, T.; Yoshida, Z. Chem. Mater. 1989,1 , 535. (b) Bryce, M. R.; Moore, A. J.; Hasan, M.; Ashwell, G. J.; Fraser, A. T.; Clegg, W.; Hursthouse, M. B.; Karaulov, A. I. Angew. Chem., Znt. Ed. Engl. 1990,29, 1450. (c) Hansen, T. K.; Lakshmikantham, M. V.; Cava, M. P.; Metzger, R. M.; Becher, J. J.Am. Chem. SOC.1991,56, 2720. (d) Benahmed-Gasmi, A. S.; Frere, P.; Garrigues, B.; Jubault, M.; Texier, F.; Gorgues, A. Tetrahedron Lett. 1992,33,6457. (4)(a) Kozaki, M.; Tnaka, S.; Yamashita, Y. J. Chem. Soc., Chem. Commun. 1992,1137. (b) Roncali, J.; Gifford, M.; Frere, P.; Jubault, M.; Gorgues, A. J. Chem. SOC.,Chem. Commun. 1993,689. (5)Dhindsa, A. S.;Song, Y. P.; Badyal, J. P.; Bryce, M. R.; Lvov, Y. M.: Pettv. M. C.: Yarwood. J. Chem. Mater. 1992.4. 724. (6)(a?Hansen, T. K.; Jorgensen, J.; Stein, P.; Becher, J. J. Org. Chem. 1992,57, 6403. (b)Hansen, T. K.; Stein, P. C. Synth. Metals 1993,55-57, 1972. @
J
NaBH3CN
I 1‘6
CF3SO3CH3
+
R
R
SeMe
HBF, 5
4 a
R
CF3S03’
6
R = SCOPh.
Scheme 2
11
a
s$-
ScMc
S 12
10
group can be removed in these products allowing alkylation of the resultant dithiolate anions. Reagent 5 has thus proved to be particularly versatile. The synthesis and reactions of reagent 5 are presented in the schemes. Our starting material was 4,5-bis(benzoylthio)-1,3-dithiole-2-thione(11, which is easily prepared in large batches.1° &Methylation of 1 using (7)Ashton, P. R.;Bissel, R. A.; Spencer, N.; Stoddart, J. F.; Tolley, M. S. Synlett 1992,923. (8) (a) Blanchard-Desce, M.; Ledoux, I.; Lehn, J. M.; Malthete, J.; Zyss, J. J. Chem. SOC.,Chem. Commun. 1988,733. (b) Sch berl, U.; Salbeck, J.; Daub, J. Adu. Mater. 1992,4 , 41. (9)(a)Yoshida, Z.;Sugimoto, T. Angew. Chem., Znt. Ed. Engl. 1988, 27,1573. (b)Schumaker, R.R.; Rajeswari, S.; Joshi, M. V.; Cava, M. P.; Takassi, M.; Metzger, R. M. J.Am. Chem. SOC.1989,111, 30. (c) Coffin, M.A.; Bryce, M. R.; Clegg, W. J.Chem. SOC.,Chem. Commun. 1992,40.
0022-326319411959-5324$04.50/00 1994 American Chemical Society
J. Org. Chem., Vol.59,No.18,1994
Synthesis of Unsymmetrical Tetrathiafulvalenes
5325
Scheme 3
14
13
methyl triflate yielded the dithiolium cation salt 2 (94% yield) which can be stored for a few weeks without decomposition. Attempted reduction of cation 2 with sodium borohydride led to extensive decomposition, whereas sodium cyanoborohydride accomplished the transformation of 2 to 4. Thioether 4 was isolated as a low melting point solid in quantitative yield and was subsequently treated with triphenylphosphine a t 0 "C, followed by addition of tetrafluoroboric acid to afford phosphonium salt 5 in 89% yield. This compound is suitable for further reactions without the need for purification, although recrystallization is profitable for obtaining a more stable, analytically pure sample of 5, which can be stored a t room temperature in the dark for several month without decomposition. The pivotal reaction in our strategy was the generation of ylide 7 from phosphonium salt 5: this is readily achieved by treatment of the latter compound with diisopropylethylamine or triethylamine in acetonitrile at room temperature. Trapping of the transient ylide 7 by the 2-(methylseleno)substituted 1,3-dithiolium cation salts 6 (prepared from 2, via selenone 3, Scheme 1>, 11, and 12 afforded TTF derivatives 8- 10, respectively, in 66-93% yield. This route represents a n improvement over the literature synthesis12 of 9 and provides a clean method of obtaining the new unsymmetrical "I'F derivatives 8 and 10. The reaction of a 1,3-dithiole Wittig (or Wittig-Horner) reagent with a 1,3-dithiolium cation has been used recently on occasion to synthesize unsymmetrical TTF derivatives.13 This methodology, which can be capricious depending upon the functionality present on the 1,3dithiole units, has the merit of avoiding the formation of mixtures of self-coupled and cross-coupledproducts which are notoriously difficult to separate.'* We have established t h a t TTF derivative 10 can be cleanly debenzoylated (Scheme 3), thereby serving as a shelf-stable equivalent of the "TF-dithiolate dianion 13.15 Treatment of 10 with sodium ethoxide in ethanol a t room temperature, followed by addition of n-propyl bromide, gave 4,5-bis(propylthio)-TTF (14) in 85% yield. The versatility of ylide 7 as a reactive intermediate in the synthesis of new 1,3-dithiol-2-ylidene derivatives has been demonstrated in the following experiments. Trapping of 7 with the appropriate aldehyde gave compounds ~~
~
~~~
~
~
(10)Steimecke, G.;Sieler, H.-J.; Kirmse, R.; Hoyer, E. Phosphorus Sulfur 1979,7 , 49. (11)Ishikawa, K.; Akiba, K.; Inamoto, N. Tetrahedron Lett. 1976, 41,3695. (12)Hansen, T.IC;Hawkins, I.; Varma, K. S.; Edge, S.; Larsen, S.; Becher, J.; Underhill, A. E. J. Chem. Soc., Perkin Duns. 2 1991,1963. (13)(a) Gonella, N. C.; Cava, M. P. J. Org. Chem. 1978,43,369. (b) Lerstrup, K.;Johannesen, I.; Jorgensen, M. Synth. Metals 1988, 27, B9. (c) Bryce, M. R.; Moore, A. J.; Lorcy, D.; Dhindsa, A. S.; Robert, A. J. Chem. SOC.,Chem. Commun. 1990,470. (d) Khodorkovsky, V. Yu.; Tormos, G. V.; Neiland, 0. Ya.; Kolotilo, N. V.; Il'chenko, A. Ya. Tetrahedron Lett. 1992,33, 973. (e) Sudmale, I. V.; Tormos, G. V.; Khodorkovsky, V. Yu.; Edzina, A. S.; Neilands, 0. J.; Cava, M. P. J. Org. Chem. 1993,58,1355. (0 Formigu, M.; Krebs, F. C.; Larsen, J. Synthesis 1993,509. (14)(a)Krief, A. Tetrahedron 1986, 42, 1209. (b) Schukat, G.; Richter, A. M.; Fanghhnel, E. Sulfur Rep. 1987,3,155. (15)For an alternative method of generating 13 in low yield see: Moore, A. J.;Bryce, M. R.; Cooke, G.; Marshallsay, G. J.;Skabara, P. J.; Batsanov, A. S.; Howard, J. A. K.; Daley, S. T.A. K.J . Chem. SOC., Perkin Trans. 1 1993,1403.
Figure 1. X-ray structure of compound 18. Scheme 4
L
RCHO
1 '
1 + phc(o)s>:>
Me>.$
MeS
18
McS
+
Mesxs$
PhC(0)S 19
20
15-17 (31-75% yield). Deprotection of compound 17 and methylation of the resultant thiolate anion species has been examined. Reaction of 17 with 2 equiv of sodium ethoxide, followed by addition of a n excess of methyl iodide, gave bis(methylthio1 derivative 18 (93% yield). The same reaction, employing only 1 equiv of ethoxide and an excess of methyl iodide, gave three products which were identified as compound 18 (25% yield) and a n unseparable mixture of the two regioisomers 19 and 20 in a 1 : l ratio as judged by lH-NMR (the combined yield of 19 and 20 is 52%). This experiment was carried out in order to investigate a possible nonbonded intramolecular interaction observed i n the solid-state structures of 17 and 18 (discussed below) which could imply restricted rotation about the bonds marked "a" (Scheme 4). I t should be noted that compound 4 could be deprotected in a manner similar to that of 1. This procedure may be relevant in cases where a desired substituent cannot withstand the methylation step. It can then be introduced a t this stage. An example of a procedure for deprotection of 4 and subsequent dialkylation with propyl bromide to afford 21 is given in the Experimental Section. The molecular structures of compounds 18 and 17, determined by single X-ray analysis,16 are shown in Figures 1and 2, respectively. Compound 18 crystallizes with two independent molecules in the unit cell, arranged in centrosymmetric dimers. Analysis of the bond lengths provides no evidence for any significant degree of in(16)Further data (including packing diagrams) on the X-ray structures of 17 and 18 have been deposited with the Cambridge Crystallographic Data Centre. The coordinates can be obtained, on request, from the Director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 lEZ, LJK.
5326
J. Org. Chem., Vol.59,No. 18,1994
Hansen et al.
d"
CHBI
"C (lit.'' mp 139-42 "C). lH-NMR (CDC13; 250 MHz) 6: 8.02 (2H,d, J = 8 Hz); 7.96(2H, d, J = 8 Hz);7.68 (2H, t, J = 8 Hz); 7.52(4H, t, J = 8 Hz). MS (E11mlz (re1 int): 454 (M+,22 (based on @"'e, the ion cluster shows the expected isotopic pattern for an ion with one selenium atom)) 330 (4);301 (10); 288 (9);160 (6);105 (100);77 (36). Preparation of 4. A fresh sample of 2 (2.85g; 5 mmol) was added portionwise t o an ice-cooled solution of sodium cyanoborohydride (0.40g; 6.5 mmol) in absolute ethanol (50 mL) under nitrogen. The solution quickly became homogeneous. After the mixture was stirred for 30 min the solvent was removed on a rotary evaporator (avoiding excess heating) and the remaining oily substance was filtered through a short silica gel column using CHzClz as eluent. After evaporation of the solvent in vacuo a pale yellow oil remained. Yield: 2.1 g (100%). This product, which was pure by TLC and lH-NMR, could be crystallized at low temperature in ether but melted at rt. lH-NMR (CDCl3; 250 MHz) 6: 7.95-7.91(4H, m), 7.637.57 (2H, m); 7.49-7.43 (4H, m); 6.22 (lH, s); 2.64 (3H, s). Anal. Calcd for C18H1402S5: C, 51.18;H, 3.32. Found: C, 51.01;H, 3.54. IR (KBr) (cm-'): 1691,1680,1675,1448, 1207, 1176. MS (CVNH3) mlz (re1 int): 423 (M HI+, 1);421 (5); 378 (5);375 (100,-CH,S); 317 (5);105 (14). (EI):375 (5); 105 (100). Preparation of 5. To an ice-cooled solution of 4 (4.2g, 10 "01) in dry ether (60mL) was added triphenylphosphine (3.0 g), and after the phosphine was dissolved completely, HBF4 (5 mL of a 54% solution in diethyl ether) was added dropwise with stirring. After the mixture was stirred for 20 min the precipitated off-white solid was filtered under suction and dried in a stream of nitrogen. Yield: 6.43 g (89%). The product was suitable for further reactions, but a more stable, analytically pure, product was obtained by additional recrystallization from acetonitrilelether. Mp: 175-76 "C. lH-NMR (CDsCN; 250 MHz) 6: 8.03-7.54(25H, m); 7.27(lH, d, JHP= 3 Hz). Anal. Calcd for C ~ ~ H Z ~ O Z S ~C,P B 58.09; F ~ : H, 3.60. Found: C, 58.15;H, 3.56. IR (KBr) (cm-l): 1685 (SI, 1439, 1207,1110 (s), 1084 (8). Preparation of 6. Compound 3 (1.0g; 2.2 mmol) and methyl triflate (0.4g; 2.4mmol) were dissolved in dry CHzClz (30mL) and stirred for 3 h. Precipitation was completed by addition of 75 mL of dry ether to afford 0.88g (65%) of 6 as an off-white solid. Mp: 131-133 "C. 'H-NMR (CD3CN; 250 MHz) 6: 8.05(4H, t, J = 7 Hz); 7.77 (2H, pentet, J = 7 Hz); 7.62 (4H, q, J = 7 Hz); 3.15 (3H, s). Anal. Calcd for (219H1305S&3eF3: C, 37.01;H, 2.11. Found: C, 37.02;H, 2.16.IR (KBr) (cm-I): 1687,1446,1198,1174. Preparation of 8. Compound 5 (250mg; 0.35mmol) and 12 (135 mg; 0.35 mmol) were dissolved in 10 mL of dry acetonitrile, and triethylamine (4 mL of a 0.1M solution in acetonitrile) was added. A dark red solid precipitated rapidly and was filtered off after 15 min and washed with a few drops of methanol. The solid (120mg 66%) was pure by NMR. An analytical sample was prepared by recrystallization from toluene. Mp: 187 "C. 'H-NMR (CDCl3; 250 MHz) 6: 8.01(d, 2H);7.8-7.1 (m, 12 H). Anal. Calcd for C24H140zS~:C, 54.75; H, 2.66. Found: C, 54.55;H, 2.64. IR (KBr) (cm-l): 1687, 1447,1206,1177,889.MS (EI) mlz (re1int): 526 (M+;3);476 (4);380 (4);301 (5); 105 (100)(-PhCO). Preparation of 9. Compounds 5 (300 mg; 0.41 mmol) and 6 (260 mg; 0.41 mmol) were mixed in acetonitrile (10 mL). Diisopropylethylamine (0.5 mL) was added t o the mixture, whereupon a red solid precipitated and was filtered off after 15 min. This solid was identical by TLC and mixed melting point to an authentic sample of 9. Yield: 250 mg (82%). Mp: 195-7 "C (lit.12mp 195 "C). Preparation of 10. To a mixture of 3 (0.25g, 0.73mmol) and 5 (0.53g; 0.73mmol) dissolved in acetonitrile (20mL) was added diisopropylethylamine (1 mL), producing an almost immediate red coloration, After 15 min the reaction mixture was diluted with CHzClz(50 mL) and then washed with water
+
Figure 2. X-ray structure of compound 17.
tramolecular charge transfer which could arise from the 1,3-dithiol-2-ylidene unit to the nitrofuran (acceptor) unit. The dithiole and furan rings are almost coplanar with a close intramolecular nonbonded contact between O ( 1 j S (1) of 2.86 (cf. t h e van der Waals radii of oxygen and sulfur which are 1.40 and 1.80 respectively). The bond lengths and angles within the nitrofuran and dithiol-2ylidene portions of compounds 17 are very similar to those of compounds 18. The nonbonded contact O ( 1 j S (2) for compound 17 is 2.82 8. An additional interesting feature of the structure of 17 is that one of the benzoylthio substituents is coplanar with the dithiole ring to which it is attached, and a close nonbonded contact, 0(2)-S(1) 2.56 is observed.
A
A,
A,
Experimental Section General. Solvents and reagents were standard reagent grade and used as received unless otherwise stated. Dry solvents were obtained by standard techniques. Preparation of 2. To a slurry of 6.5g (16.0mmol) of 43bis(benzoylthio)-1,3-dithiole-2-thione in 60 mL of CHzClz was added 2.9 g (17.7nmole) of methyl triflate. After 1-2 h of stirring the solution became homogeneous, but stirring was continued for a further 3-4 h. The solvent was partially removed under vacuum until precipitation started, and then a layer of dry diethyl ether (100mL) was placed on top of the CHzClz layer. The two layers mixed overnight and completed precipitation. A pale yellow solid was filtered off and dried. Yield: 8.6g (94%). The compound was best used within a few weeks. Recrystallization from acetonitrilelether gave an analytically pure product. Mp: 185-86 "C. 'H-NMR (CD3CN; 250 MHz) 6: 8.07(4H, d, J = 9 Hz); 7.82(2H,t, J = 9 Hz); 7.64(4H, t, J = 9 Hz); 3.21(3H, s). Anal. Calcd for (319H1305S6F3: C, 40.14;H, 2.28. Found: C, 40.44;H, 2.13. IR (KBr) (cm-'): 1689,1259,1208,1030. Preparation of 3. A mixture of finely powdered elemental selenium (1.8g; 23 mmol) and powdered sodium borohydride (1.0g; 27 mmol) was stirred as a slurry in dry 2-propanol (30 mL) under nitrogen. After 90 min the mixture was homogeneous and colorless. THen 3.0 g of freshly prepared 2 was added and the reddish mixture was stirred for 20 min whereupon benzoyl chloride (4mL) was added and the mixture was left with stirring for a further 1 h. Water (50mL) was added to the mixture which subsequently was extracted with three portions of CHZC12. After the organic phase was dried with MgS04 the solvent was partly removed under vacuum until precipitation started. Addition of methanol completed precipitation of a red solid. Yield: 1.8 g (76%). Mp: 165-7
(17) (a) Khodorkovsky, V. Yu.;Kreicberga, Ya.N.;Balodis, K. A.; Neiland, 0. Ya.Isv. Akad. Nauk. SSSR,Khim. Ser. 1988,120. (b) Cornelissen, J. P. Dissertation, Rijksuniversiteit Leiden, 1992, p 91.
Synthesis of Unsymmetrical Tetrathiafulvalenes (3 x 25 mL), dried with MgS04, and evaporated under vacuum. The residue was chromatographed on a silica gel column using a CHzCldhexane (1:3) mixture as eluent. The red iodine-active fraction was evaporated to afford a dark red solid, which afforded red crystals from hot dichlorobenzene. Yield: 120 mg (35%). Mp: 180 "C. 'H-NMR (CDCl3;250 MHz) 6: 7.95-7.26 (lOH, m); 6.3 (2H, SI. Anal. Calcd for CzoHlzOzSs: C, 50.41; H, 2.52. Found: C, 50.09; H, 2.49. IR (KBr) (cm-I): 1688, 1636, 1207,1178. MS (CI/NH3): 477 ((M + HI+, 11);337 (11); 267 (6); 243 (22); 237 (14); 122 (30); 105 (100). Preparation of 11. Four hundred mg (1.9 mmol) of 1,3dithi0le-2-selenone'~~J~ was dissolved in 10 mL of CHZC12, and 0.33 g (2.0 mmol) of methyl triflate was added. The mixture was stirred overnight, and then 40 mL of dry ether was added to precipitate an off-white crystalline solid which was filtered and dried under nitrogen. Yield: 600 mg (92%). Mp: 154 "C. 'H-NMR (CD3CN 250 MHz) 6: 8.77 (2H, 9); 3.11(3H, s). Anal. Calcd for C5H5S3Se03F3:C, 17.64; H, 1.45. Found: C, 18.07; 1032 (8). H, 1.58. IR (KBr) (cm-'): 1279 (9); 1235 (4; Preparation of 12. Benzo[cl-1,3-dithiole-2-selenone(2.3 g, 10 mmol) was dissolved in dry CHzClz (15 mL), and methyl triflate (2.0 g, 1.2 mmol) was added. After 3 h dry ether (50 mL) was added slowly with stirring to precipitate an orange crystalline solid (3.7 g, 93%). Mp: 167 "C. 'H-NMR (CDaCN, 250 MHz) 6: 8.46 (dd, 2H, J , = 8 Hz; Jb = 3 Hz); 7.91 (dd, 2H, J , = 8 Hz; Jb = 3 Hz); 3.23 (s, 3H). Anal. Calcd for CgH703F3S3Se: C, 27.34; H, 1.77. Found: C, 27.18; H, 1.79. Preparation of 14. Compound 10 (600 mg; 1.3 mmol) was dissolved in dry THF (25 mL) under nitrogen, and sodium ethoxide (prepared from 75 mg of sodium dissolved in 10 mL of absolute ethanol, 2.5 equiv) was added. After 10 min of stirring n-propyl bromide (1 mL) was added t o the dark solution which was stirred for a further 1h. After evaporation of the solvent, the residue was chromatographed on silica gel using CHzClhexane as eluent (1:3). The yellow, iodine-active fraction was an oil (380 mg, 85%)after drying in vacuo. The compound was pure by 'H-NMR. lH-NMR (CDCL; 250 MHz) 6: 6.32 (2H, s), 2.79 (4H, t, J = 7 Hz), 1.67 (4H, m), 1.04 (6H, t, J = 7 Hz). MS (E11 mlz (re1 int) 352 (100); 309 (27); 276 (44); 267 (40); 244 (10); 179 (19); 146 (93); 102 (32). HRMS: calcd mlz 351.95763; found mlz 351.95296. Preparation of 15. Compound 5 (500 mg; 0.69 mmol) and 4-nitrobenzaldehyde (150 mg; 1.0 mmol) was dissolved in acetonitrile (15 mL), and diisopropylethylamine (1 mL) was added. A yellow crystalline solid precipitated, which was dried to afford 150 mg (43%)of 15. It was possible to recover 2025% more of 15 from the mother liquor, using chromatography (CHZC12 as eluent, silica gel as stationary phase). Mp: 17275 "C. 'H-NMR (CDC13;250 MHz) 6: 8.41-7.31 (14H; m), 6.61 (lH, s). AnaI. Calcd for C24H1604NS4: C, 56.58; H, 2.95; N, 2.75. Found: C, 56.31; H, 3.26; N, 2.52. IR (KBr) (cm-l): 1685, 1439, 1207, 1110, 1084. MS (CI/NH3)mlz (re1 int): 510 ((M H)+,5); 374 (51); 344 (10);243 (24); 240 (7); 150 (6); 122 (31);105 (100). Preparation of 16. Compound 5 (200 mg; 0.28 mmol) was dissolved in acetonitrile (5 mL) with 5-formylthiadiazo1el9(50 mg; 0.4 mmol) and triethylamine (0.25 mL). A yellow solid precipitated immediately. Yield: 40 mg (31%). In the solid state the compound is stable, but in basic solution it decomposed in less than 1 h. Mp: 194-95 "C. 'H-NMR (CDCl3; 250 MHz) 6: 8.11 (lH, s); 7.95 (4H, d, J = 7.9 Hz); 7.63 (2H; t, J = 7.9 Hz); 7.48 (4H, t, J = 7.9 Hz); 6.87 (lH, 8 ) . Anal. Calcd for CZoH12S602N2: C, 50.85; H, 2.54; N, 5.93. Found: C, 51.03; H, 2.66; N, 5.76. MS: neither E1 nor CI ionization gave an M+ ion. Both spectra were dominated by mlz 105 (loss of PhCO).
+
(18)Engler, E.; Patel, V. J . Org.Chem. 1976, 40(3), 387. (19) Kobori, T.;Fujita, M.; Hiyama, T.; Kondo, K. Synlett 1992,95.
J. Org. Chem., Vol. 59, No. 18, 1994 5327 Preparation of 17. Wittig-reagent 5 (1.12 g; 1.5 mmol) and 5-nitrofurfural (0.2 g; 1.5 mmol) were dissolved in dry acetonitrile (10 mL) and treated with diisopropylethylamine (1 mL). A deep-red solid precipitated and was filtered off. Yield: 0.58 g (75%). Mp: 215-6 "C. 'H-NMR (CDCl3; 250 MHz) 6: 7.93-7.44 (lOH, arom mult); 7.38 (lH, d, J = 3.9 Hz); 6.47 (lH, s); 6.27 (lH, d, J = 3.9 Hz). Anal. Calcd for C22H13NO&4:C, 52.91; H, 2.61; N, 2.81. Found: C, 53.22; H, 2.69; N, 2.96. IR (KBr) (cm-l): 1692, 1585, 1484, 1449, 1348, 1239, 1206, 1175. MS: no M+ ion was observed in E1 or CI (NH3) mass spectrometry. Preparation of 18. Compound 17 (160 mg; 0.32 mmol) was dissolved in dry THF (25 mL) under nitrogen with stirring. A solution of sodium ethoxide in absolute ethanol (8 mL; 0.1 M) was added all at once. The solution turned from dark reddish to very dark blue immediately. After 5 min methyl iodide (0.5 mL) was added, and the solution became deep red after a few minutes. After an additional 15 min of stirring the solvent was removed in vacuo, and the residue was dissolved in the minimum amount of CHzClz and chromatographed on a short silica gel column using CHzClz as eluent. The strongly colored fraction was collected and afforded a dark green solid 18 (95 mg, 93%yield) which was pure by TLC (the color was red-violet on the TLC plates and in solution). Metallic-green crystals of X-ray quality were grown by cooling a hot solution of 18 in acetonitrile. Mp: 180-81 "C. lH-NMR (CDC13; 250 MHz) 6: 7.40 (lH, d, J = 4.8 Hz); 6.40 (1H s); 6.25 (lH, d, J = 4.8 Hz); 2.50 (3H, 9); 2.47 (3H, s). Anal. Calcd for C10H903NS4: C, 37.61; H, 2.82; N, 4.39. Found: C, 37.70; H, 2.82; N, 4.28. MS (EI)mlz (re1 int): 319 (M+, 100); 288 (40); 274 (5); 245 (2); 242 (2); 94 (3). Preparation of 19 and 20. The procedure was similar to the one used for 18 starting with 17 (160 mg) but using only 1 equiv of sodium ethoxide. Separation of three colored fractions was achieved using a silica column and toluene as eluent. The first fraction was solid 18 (26 mg; 25%), and the second (a deep red oil) was the desired monoprotected mixture (68 mg, 52%) which consisted as a 1:l mixture (from NMR) of the two regioisomers 19 and 20. Although the spots of the mixture were elongated on analytical TLC-plates indicating the presence of two isomers, a preparative scale separation could not be achieved. The third colored fraction (18 mg; 11%) was starting material 17. lH-NMR (CDCl3;500 MHz) 6: 7.98 (4H, dd, J , = 7.5 Hz; Jb = 4 Hz); 7.66 (2H, t, J = 7.5 Hz); 7.52 (4H, t, J = 7.4 Hz); 7.41 (lH, d, J = 4.0 Hz); 7.39 (lH, d, J = 4.0 Hz); 6.44 (lH, s); 6.42 (lH, s); 6.27 (lH, d, J = 4.0 Hz); 6.25 (lH, d, J = 4.0 Hz); 2.56 (3H, s); 2.49 (3H, s). MS (CV NH3) mlz (re1 int): 410 ([M HI+, 8); 275 (10); 274 (15); 135 (10); 139 (32); 122 (100); 105 (35); 78 (12). Preparation of 2-(Methylsulfanyl)-4,5-bis(propylsulfanyl)[l,3ldithiole(21). Compound 4 (850 mg, 2.0 mmol) was dissolved in dry THF (10 mL) and kept under nitrogen. A solution of sodium ethoxide in ethanol (25 mL; 0.1 M) was added. The solution turned dark immediately, and after 5 min n-propyl bromide (0.5 mL) was added. Chromatographic workup using a 1:l mixture of hexaneICHzCl2 as eluent and silica gel as stationary phase afforded 21 as a yellow oil which was pure by NMR. Yield: 400 mg (67%). 'H-NMR (CDCl3; 250 MHz) 6: 5.76 (lH, s); 2.49-2.88 (2H, mult); 2.72-2.61 (2H, mult); 2.25 (3H, s); 1.77-1.60 (4H, mult); 1.01 (6H, t, J = 7.4 Hz). MS (EI) 298 (M+,21); 251 (100);209 (14); 167 (13); 119 (9); 105 (17); 45 (20); 43 (85); calcd 298.00121, found 298.00123.
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Acknowledgment. We thank SERC, NATO, NovoNordisk, The Royal Society and the Danish Natural Science Research Council (SNF)for funding this work. A sample of 5-formyl-thiadiazole was kindly provided by Dr. Wim Dehaen, University of Leuven.
